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PR01532

Identifier
CXCCHMKINER3  [View Relations]  [View Alignment]  
Accession
PR01532
No. of Motifs
9
Creation Date
05-JUN-2001
Title
C-X-C chemokine receptor type 3 signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR00657 CCCHEMOKINER
Literature References
1. ATTWOOD, T.K. AND FINDLAY, J.B.C. 
Fingerprinting G protein-coupled receptors.
PROTEIN ENG. 7(2) 195-203 (1994).
 
2. ATTWOOD, T.K. AND FINDLAY, J.B.C. 
G protein-coupled receptor fingerprints.
7TM, VOLUME 2, EDS. G.VRIEND AND B.BYWATER (1993).
 
3. BIRNBAUMER, L.
G proteins in signal transduction.
ANNU.REV.PHARMACOL.TOXICOL. 30 675-705 (1990).
 
4. CASEY, P.J. AND GILMAN, A.G.
G protein involvement in receptor-effector coupling.
J.BIOL.CHEM. 263(6) 2577-2580 (1988).
 
5. ATTWOOD, T.K. AND FINDLAY, J.B.C. 
Design of a discriminating fingerprint for G protein-coupled receptors.
PROTEIN ENG. 6(2) 167-176 (1993).
 
6. WATSON, S. AND ARKINSTALL, S.
Chemokines.
IN THE G protein-LINKED RECEPTOR FACTSBOOK, ACADEMIC PRESS, 1994, PP.83-88.
 
7. LOETSCHER, M., GERBER, B., LOETSCHER, P., JONES, S.A., PIALI, L.,
CLARK-LEWIS, I., BAGGIOLINI, M. AND MOSER, B. 
Chemokine receptor specific for IP10 and mig: structure, function, and
expression in activated T-lymphocytes.
J.EXP.MED. 184(3) 963-969 (1996).
 
8. COLE, K.E., STRICK, C.A., PARADIS, T.J., OGBORNE, K.T., LOETSCHER, M.,
GLADUE, R.P., LIN, W., BOYD, J.G., MOSER, B., WOOD, D.E., SAHAGAN, B.G.
Interferon-inducible T cell alpha chemoattractant (I-TAC): a novel non-ELR
CXC chemokine with potent activity on activated T cells through selective
high affinity binding to CXCR3.
J.EXP.MED. 187(12) 2009-2012 (1998).
 
9. GARCIA-LOPEZ, M.A., SANCHEZ-MADRID, F., RODRIGUEZ-FRADE, J.M.,
MELLADO, M., ACEVEDO, A., GARCIA, M.I., ALBAR, J.P., MARTINEZ, C.
AND MARAZUELA, M.
CXCR3 chemokine receptor distribution in normal and inflamed tissues:
expression on activated lymphocytes, endothelial cells, and dendritic cells.
LAB.INVEST. 81(3) 409-418 (2001).
 
10. COX, M.A., JENH, C.H., GONSIOREK, W., FINE, J., NARULA, S.K.,
ZAVODNY, P.J. AND HIPKIN, R.W.
Human interferon-inducible 10-kDa protein and human interferon-inducible T
cell alpha chemoattractant are allotropic ligands for human CXCR3: a
differential binding to receptor states.
MOL.PHARMACOL. 59(4) 707-715 (2001).
 
11. WENG, Y., SICILIANO, S.J., WALDBURGER, K.E., SIROTINA-MEISHER, A.,
STARUCH, M.J., DAUGHERTY, B.L., GOULD, S.L., SPRINGER, M.S. AND
DEMARTINO, J.A.
Binding and functional properties of recombinant and endogenous CXCR3
chemokine receptors.
J.BIOL.CHEM. 273(29) 18288-18291 (1998).
 
12. WANG, X., LI, X., SCHMIDT, D.B., FOLEY, J.J., BARONE, F.C., AMES, R.S.
AND SARAU, H.M.
Identification and molecular characterization of rat CXCR3: receptor
expression and interferon-inducible protein-10 binding are increased in
focal stroke.
MOL.PHARMACOL. 57(6) 1190-1198 (2000).

Documentation
AND NEOTE, K.
G protein-coupled receptors (GPCRs) constitute a vast protein family that
encompasses a wide range of functions (including various autocrine, para-
crine and endocrine processes). They show considerable diversity at the
sequence level, on the basis of which they can be separated into distinct
groups. We use the term clan to describe the GPCRs, as they embrace a group
of families for which there are indications of evolutionary relationship,
but between which there is no statistically significant similarity in
sequence [1]. The currently known clan members include the rhodopsin-like
GPCRs, the secretin-like GPCRs, the cAMP receptors, the fungal mating
pheromone receptors, and the metabotropic glutamate receptor family.
 
The rhodopsin-like GPCRs themselves represent a widespread protein family
that includes hormone, neurotransmitter and light receptors, all of
which transduce extracellular signals through interaction with guanine
nucleotide-binding (G) proteins. Although their activating ligands vary
widely in structure and character, the amino acid sequences of the 
receptors are very similar and are believed to adopt a common structural
framework comprising 7 transmembrane (TM) helices [3-5].
 
Chemokines are proteins that have important physiological and patho-
physiological roles in a wide range of acute and chronic inflammatory
processes [6]. Their sequences are similar and are characterised by a
4-cysteine motif: the family can be divided according to whether the first 2
Cys residues are adjacent (the C-C family), or separated by an intervening
residue (the C-x-C family).
 
The C-X-C chemokines IP10, Mig and I-TAC are upregulated in response to
interferon-gamma and are potent chemoattractants for activated T cells
[8,11]. All three chemokines have been found to activate the type 3 C-X-C
chemokine receptor (CXCR3) [7,8]. CXCR3 is expressed in natural killer cells
and activated T lymphocytes but not in resting T lymphocytes, B lymphocytes,
monocytes or granulocytes [7]. CXCR3 also appears to be constitutively
expressed on endothelial cells of medium and large blood vessels [9]. Upon
binding to CXCR3, all three ligands cause mobilisation of intracellular
calcium and chemotaxis. I-TAC, however, has a much higher affinity for the
receptor and produces more potent effects than IP10 or Mig [8]. I-TAC
appears to bind to two distinct sites on CXCR3: when the receptor is in the
active conformation, all three ligands can bind, but I-TAC binds at an
allotropic site, distinct from that of IP10 and Mig. By contrast, only I-TAC
can bind to the uncoupled conformation of the receptor [10]. CXCR3 is also
capable of binding a number of CC chemokines with moderate affinity. One of
these, eotaxin, appears to act as a natural antagonist of the receptor [11].
 
The main role of CXCR3 and its ligands appears to be the selective
recruitment of effector T cells in both normal tissues and inflammation [8].
CXCR3 may be involved in a number of T cell-mediated inflammatory diseases,
such as autoimmune diseases, delayed-type hypersensitivity responses,
certain viral diseases and transplant rejection. Upregulation of I-TAC in
astrocytes and microglial cells by interferon suggests that it may also play
a role in neuroinflammatory diseases, such as meningitis, encephalitis and
multiple sclerosis [8]. IP10 has also been suggested to be involved in
recruitment of inflammatory cells into the brain following ischaemic injury
[12].
 
CXCCHMKINER3 is a 9-element fingerprint that provides a signature for the
type 3 C-X-C chemokine receptor. The fingerprint was derived from an initial
alignment of 4 sequences: the motifs were drawn from conserved regions
spanning the full alignment length, focusing on those sections that
characterise the type 3 C-X-C chemokine receptors but distinguish them
from other members of the chemokine receptor family - motifs 1-3 reside at
the N-terminus; motif 4 spans the first cytoplasmic loop, leading into TM
domain 2; motif 5 encodes the second cytoplasmic loop; motif 6 spans the
C-terminal portion of TM domain 4; motif 7 lies in the second external loop;
motif 8 lies in the third external loop, leading into TM domain 7; and motif
9 resides at the C-terminus. A single iteration on SPTR39_15f was required
to reach convergence, no further sequences being identified beyond the 
starting set.
Summary Information
4 codes involving  9 elements
0 codes involving 8 elements
0 codes involving 7 elements
0 codes involving 6 elements
0 codes involving 5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
9444444444
8000000000
7000000000
6000000000
5000000000
4000000000
3000000000
2000000000
123456789
True Positives
CCR3_HUMAN    O88410        Q9JII9        Q9QWN6        
Sequence Titles
CCR3_HUMAN  C-C chemokine receptor type 3 (C-C CKR-3) (CC-CKR-3) (CCR-3) (CCR3) (CKR3) (Eosinophil eotaxin receptor) (CD193 antigen) - Homo sapiens (Human). 
O88410 CHEMOKINE RECEPTOR CXCR3 - MUS MUSCULUS (MOUSE).
Q9JII9 CHEMOKINE RECEPTOR CXCR3 - Rattus norvegicus (Rat).
Q9QWN6 INTERFERON-INDUCIBLE PROTEIN 10 RECEPTOR - Mus musculus (Mouse).
Scan History
SPTR39_15f 1  150  NSINGLE    
Initial Motifs
Motif 1  width=20
Element Seqn Id St Int Rpt
LEVSERQVLDASDFAFLLEN Q9QWN6 3 3 -
LEVSERQVLDASDIAFLLEN Q9JII9 3 3 -
LEVSDHQVLNDAEVAALLEN CCR3_HUMAN 3 3 -
LEVSERQVLDASDFAFLLEN O88410 3 3 -

Motif 2 width=12
Element Seqn Id St Int Rpt
SPYDYGENESDF Q9JII9 25 2 -
SSYDYGENESDS CCR3_HUMAN 25 2 -
SPYDYGENESDF O88410 25 2 -
SPYDYGENESDF Q9QWN6 25 2 -

Motif 3 width=14
Element Seqn Id St Int Rpt
SPPCPQDFSLNFDR CCR3_HUMAN 40 3 -
SPPCPQDFSLNFDR O88410 39 2 -
SPPCPQDFSLNFDR Q9QWN6 39 2 -
SPPCPQDFSLNFDR Q9JII9 39 2 -

Motif 4 width=12
Element Seqn Id St Int Rpt
LSQRTALSSTDT Q9JII9 78 25 -
LSQRTALSSTDT Q9QWN6 78 25 -
LSQRTALSSTDT O88410 78 25 -
LSRRTALSSTDT CCR3_HUMAN 79 25 -

Motif 5 width=13
Element Seqn Id St Int Rpt
SIVHATQIYRRDP Q9QWN6 151 61 -
SIVHATQIYRRDP Q9JII9 151 61 -
NIVHATQLYRRGP CCR3_HUMAN 152 61 -
SIVHATQIYRRDP O88410 151 61 -

Motif 6 width=16
Element Seqn Id St Int Rpt
WGLCLLFALPDFIYLS O88410 175 11 -
WGLCVLFALPDFIFLS Q9JII9 175 11 -
WGLCLLFALPDFIFLS CCR3_HUMAN 176 11 -
WGLCLLFALPDFIYLS Q9QWN6 175 11 -

Motif 7 width=13
Element Seqn Id St Int Rpt
QYNFPQVGRTALR CCR3_HUMAN 204 12 -
QYNFPQVGRTALR O88410 203 12 -
QYNFPQVGRTALR Q9QWN6 203 12 -
QYNFPQVGRTALR Q9JII9 203 12 -

Motif 8 width=17
Element Seqn Id St Int Rpt
GRKSHVDVAKSVTSGMG O88410 290 74 -
GRESHVDVAKSVTSGMG Q9JII9 290 74 -
GRESRVDVAKSVTSGLG CCR3_HUMAN 291 74 -
GRESHVDVAKSVTSGMG Q9QWN6 290 74 -

Motif 9 width=16
Element Seqn Id St Int Rpt
RRESSWSETTEASYLG O88410 351 44 -
RRESSWSETTEASYLG Q9JII9 351 44 -
RRESSWSETTEASYLG Q9QWN6 351 44 -
RRDSSWSETSEASYSG CCR3_HUMAN 352 44 -
Final Motifs
Motif 1  width=20
Element Seqn Id St Int Rpt
LEVSERQVLDASDFAFLLEN Q9QWN6 3 3 -
LEVSERQVLDASDIAFLLEN Q9JII9 3 3 -
LEVSDHQVLNDAEVAALLEN CCR3_HUMAN 3 3 -
LEVSERQVLDASDFAFLLEN O88410 3 3 -

Motif 2 width=12
Element Seqn Id St Int Rpt
SPYDYGENESDF Q9JII9 25 2 -
SSYDYGENESDS CCR3_HUMAN 25 2 -
SPYDYGENESDF O88410 25 2 -
SPYDYGENESDF Q9QWN6 25 2 -

Motif 3 width=14
Element Seqn Id St Int Rpt
SPPCPQDFSLNFDR CCR3_HUMAN 40 3 -
SPPCPQDFSLNFDR O88410 39 2 -
SPPCPQDFSLNFDR Q9QWN6 39 2 -
SPPCPQDFSLNFDR Q9JII9 39 2 -

Motif 4 width=12
Element Seqn Id St Int Rpt
LSQRTALSSTDT Q9JII9 78 25 -
LSQRTALSSTDT Q9QWN6 78 25 -
LSQRTALSSTDT O88410 78 25 -
LSRRTALSSTDT CCR3_HUMAN 79 25 -

Motif 5 width=13
Element Seqn Id St Int Rpt
SIVHATQIYRRDP Q9QWN6 151 61 -
SIVHATQIYRRDP Q9JII9 151 61 -
NIVHATQLYRRGP CCR3_HUMAN 152 61 -
SIVHATQIYRRDP O88410 151 61 -

Motif 6 width=16
Element Seqn Id St Int Rpt
WGLCLLFALPDFIYLS O88410 175 11 -
WGLCVLFALPDFIFLS Q9JII9 175 11 -
WGLCLLFALPDFIFLS CCR3_HUMAN 176 11 -
WGLCLLFALPDFIYLS Q9QWN6 175 11 -

Motif 7 width=13
Element Seqn Id St Int Rpt
QYNFPQVGRTALR CCR3_HUMAN 204 12 -
QYNFPQVGRTALR O88410 203 12 -
QYNFPQVGRTALR Q9QWN6 203 12 -
QYNFPQVGRTALR Q9JII9 203 12 -

Motif 8 width=17
Element Seqn Id St Int Rpt
GRKSHVDVAKSVTSGMG O88410 290 74 -
GRESHVDVAKSVTSGMG Q9JII9 290 74 -
GRESRVDVAKSVTSGLG CCR3_HUMAN 291 74 -
GRESHVDVAKSVTSGMG Q9QWN6 290 74 -

Motif 9 width=16
Element Seqn Id St Int Rpt
RRESSWSETTEASYLG O88410 351 44 -
RRESSWSETTEASYLG Q9JII9 351 44 -
RRESSWSETTEASYLG Q9QWN6 351 44 -
RRDSSWSETSEASYSG CCR3_HUMAN 352 44 -